crossing96/oncoscreening huggingface dataset:
Ozone aging amplifies the tumor-promoting effects associated with low-dose graphene oxide exposure in bladder tumors via the integrin αV signaling pathway.	With the rapid expansion of industrial and commercial applications, graphene-based 2D nanomaterials such as graphene oxide (GO) are increasingly released into the environment, raising concerns about their environmental accumulation and the likelihood of human exposure. While previous studies have primarily focused on the cytotoxic effects of pristine GO (P-GO) at high exposure doses, the biological effects of GO under real environmental conditions remain poorly understood. Notably, atmospheric environmental media, such as ozone, can significantly alter the physicochemical properties of GO, thereby modulating its biological effects. In this study, we employed a non-direct toxicity dose to demonstrate that ozone aging can significantly modify the physicochemical properties of GO and enhance its low-dose exposure-mediated pro-tumor progression effect. Mechanistically, ozone-aged GO (O-GO) treatment increases the membrane localization of integrin αV, leading to the activation of the PI3K/AKT/mTOR signaling pathway, which drives bladder tumor proliferation. Furthermore, O-GO enhances the TGF-β signaling pathway by upregulating the expression levels of the TGF-β receptor, promoting bladder tumor cell invasiveness and metastasis. These findings provide novel insights into the tumor-promoting effects of GO at non-direct toxicity dose and emphasize the necessity of considering environmental aging process when assessing its environmental health and safety (EHS) risks. Given the expanding use of graphene-based materials in daily human life, our study highlights the urgent need for greener development strategies to mitigate potential health risks associated with GO exposure.	bladder
An interpretable machine learning model based on CT imaging for predicting lymphovascular invasion and survival in bladder urothelial carcinoma: a multicenter study.	BACKGROUND: Lymphovascular invasion (LVI) is a critical prognostic factor in bladder cancer, affecting recurrence, survival, and overall prognosis. Traditional methods for diagnosing LVI, such as immunohistochemical staining, are costly and time-consuming, making non-invasive alternatives like radiomics-based models valuable. This study aimed to construct an interpretable machine learning model to predict LVI status and survival outcomes in patients with bladder urothelial carcinoma using preoperative CT images. METHODS: This study retrospectively enrolled patients with urothelial carcinoma who underwent radical cystectomy and preoperative contrast-enhanced CT from three medicine centers. Tumor regions were manually segmented, and radiomics features were extracted and selected through reproducibility testing, correlation analysis, and LASSO. Based on the selected radiomics features, machine learning classifiers, including SVM, were trained using five-fold cross-validation. A combined model was then constructed by integrating the radiomics signature with clinical risk factors. Model performance was evaluated by AUC, ACC, sensitivity, specificity, and survival analysis. RESULTS: The SVM model showed high performance, with an AUC of 0.944 in the training set and 0.872 in the testing set. The combined model integrating clinical factor performed better, achieving an AUC of 0.952 in the training set and 0.901 in the testing set. The model's interpretability was enhanced using SHAP analysis, identifying key radiomics features associated with LVI, such as tumor shape and texture. Survival analysis indicated that patients predicted to be LVI-negative had significantly better disease-free survival compared to patients predicted to be LVI-positive. CONCLUSIONS: This multicenter study demonstrates that the interpretable machine learning model based on preoperative CT images can effectively predict LVI status and survival outcomes in bladder urothelial carcinoma. TRIAL REGISTRATION: This study was retrospectively registered by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Approval No. K2024-187-01) on April 12, 2024, and informed consent was waived.	bladder
Intercept Estimation of Semi-Parametric Joint Models in the Context of Longitudinal Data Subject to Irregular Observations.	Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi-parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicative link function. Semi-parametric joint models define an intercept function as the mean outcome when all covariates are set to zero; this is differenced out in the course of estimation and is consequently not estimated. The Sun estimator thus provides estimates of relative covariate effects, but is unable to provide estimates of absolute effects or of longitudinal prognosis in the absence of covariates. We extend the Sun model by additionally estimating the intercept term, showing that our extended estimator is consistent and asymptotically Normal. In simulations, our estimator outperforms the original Sun estimator in terms of bias and standard error and is also more computationally efficient. We apply our estimator to a longitudinal study of tumor recurrence among bladder cancer patients. Provided the intercept term can be adequately captured using splines, we recommend that our extended Sun estimator be used in place of the original estimator, since it leads to smaller bias, smaller standard errors, and allows estimation of the mean outcome trajectories.	bladder
Network toxicology analysis of hair dye components and their association with breast and bladder cancers.	This study employed a network toxicology approach to investigate the potential toxic effects and molecular mechanisms of hair dye components in relation to breast and bladder cancer. By integrating data from multiple databases and performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, key targets and pathways were identified. Network and molecular docking analyses revealed that major hair dye chemicals may induce carcinogenesis through xenobiotic metabolism and interact with critical proteins involved in cancer pathways. These findings provide theoretical support for the health risks associated with hair dye exposure and offer insights into potential preventive strategies.	bladder
Clinicopathologic, immunohistochemical and genomic characterization of urothelial carcinoma with myxoid and chordoid features.	AIMS: To comprehensively characterize the clinicopathologic, immunohistochemical and genomic features of urothelial carcinoma with myxoid and chordoid features (UCMC), a rare histologic subtype of urothelial carcinoma with fewer than 50 reported cases in the literature. METHODS AND RESULTS: We retrospectively identified and analysed eight cases of UCMC using clinicopathologic information, immunohistochemistry and molecular profiling by DNA next-generation sequencing. Genomic analysis revealed a heterogeneous molecular profile, with alterations previously implicated in urothelial carcinoma, including p53/Rb/cell cycle pathway genes (6/7 cases), histone modification genes (6/7 cases) and FGFR3/PIK3CA signalling pathway genes (5/7 cases). Actionable variants were present in 6/7 cases. Classification utilizing immunohistochemical surrogates for basal and luminal subtypes of urothelial carcinoma demonstrated mixed subtypes: three cases with a luminal profile, one case with a basal profile, two cases which were double negative and two cases with a non-specific profile. One case demonstrated a molecular and immunohistochemical profile consistent with plasmacytoid urothelial carcinoma, suggesting that myxoid and chordoid features may overlap with previously recognized histologic subtypes. The five-year overall survival rate was 75%, with varying stages at presentation (pT1-pT3). CONCLUSIONS: UCMC represents a rare histologic finding, which can be associated with multiple molecular subtypes of urothelial carcinoma and can pose a diagnostic dilemma when identifying potentially aggressive histologic subtypes. It is uncertain whether UCMC represents a distinct histologic subtype, or (more likely) a histologic pattern acquired during tumour evolution. Further investigation is needed to fully understand the biological and clinical significance of this histologic pattern.	bladder
Antibody-drug conjugates for non-muscle invasive bladder cancer: current status and future development.	PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) have recently emerged as a promising targeted therapeutic strategy in urothelial carcinoma, and their application in nonmuscle invasive bladder cancer (NMIBC) is an evolving frontier. This review is timely as it synthesizes recent advances in ADC development for NMIBC, addressing critical unmet needs among both Bacillus Calmette-Guérin (BCG) naïve high-risk and BCG-unresponsive patients. RECENT FINDINGS: The literature reveals that ADCs that target HER2, Trop-2, Nectin-4 are under active investigation. Several retrospective and prospective studies have reported encouraging complete response rates, durable event-free survival, and manageable safety profiles with these agents. Current clinical trials are evaluating ADCs as monotherapy or in combination with immune checkpoint inhibitors (e.g., durvalumab, tislelizumab) and intravesical therapies, aiming to refine dosing regimens and maximize therapeutic efficacy. SUMMARY: The findings underscore the potential of ADCs to revolutionize NMIBC management by providing novel bladder-sparing strategies in patients traditionally limited by BCG failure. Future research should concentrate on optimizing patient selection, treatment sequencing, and combination strategies to improve long-term outcomes, enhancing survival and quality of life.	bladder
Global, regional, and national burden and trends of bladder cancer in individuals aged 55 years and older from 1990 to 2021: findings from the Global Burden of Disease Study 2021.	BACKGROUND: Bladder cancer (BC), a prevalent genitourinary malignancy, poses a substantial threat to public health, particularly among middle-aged and elderly populations. Given the increasing life expectancy, understanding the BC burden in these demographic groups is imperative. METHODS: Based on the GBD 2021 dataset encompassing 371 diseases and injuries with 88 risk factors globally, this study analyzed bladder cancer data from 204 countries and territories (1990-2021) for populations aged ≥55 years, with core metrics including incidence, deaths, and disability-adjusted life years (DALYs). We used Joinpoint regression analysis to assess temporal trends, calculating the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC). We conducted a decomposition analysis to break down the changes in mortality rates into contributions from aging, population growth, and epidemiological changes. We performed a frontier analysis using the Socio-demographic Index (SDI) to evaluate the relationship between bladder cancer burden in people aged 55 and above and socio-demographic development. Among them, we further combined the National Health and Nutrition Examination Survey (NHANES) database for risk analysis related to bladder cancer. Finally, we used the Bayesian age-period-cohort (BAPC) model to project bladder cancer trends from 2022 to 2036. RESULTS: From 1990 to 2021, bladder cancer cases among adults ≥55 years increased by 113% (226 421 to 483 234), while crude incidence rates declined slightly. Mortality rates decreased from 16.83 to 14.11 per 100 000, and DALYs rates dropped from 337.59 to 257.76. High-income regions (North America: 76.85/100 000; Western Europe: 77.62/100 000) had the highest incidence but showed downward trends, whereas Central Europe experienced rising mortality. Males consistently bore a 3.8-fold higher incidence burden than females. Smoking (26.6%) and high fasting glucose (8.2%) were key risk factors. According to NHANES data, elevated fasting blood glucose levels and smoking are both associated with an increased risk of bladder cancer. Projections to 2036 suggest continued declines: incidence (-13.3%), mortality (-16.4%), and DALYs (-17.9%). Health inequality persisted but improved marginally. CONCLUSION: The current data and future prediction of this study show that the incidence rate, mortality and DALYs rate of bladder cancer in middle-aged and elderly people have declined. However, disparities in disease burden still exist across regions. Thus, tailored measures are needed to reduce inequalities in high-burden areas.	bladder
The value of maintenance therapy in intermediate-risk non-muscle-invasive bladder cancer.	OBJECTIVE: To evaluate which subgroups of patients with intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) benefit from maintenance therapy based on the International Bladder Cancer Group (IBCG) risk stratification, as the role of a maintenance course in patients with IR-NMIBC is debated. PATIENTS AND METHODS: We relied on a prospectively maintained database of patients with IR-NMIBC who received intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) (2010-2023). Patients were stratified according the IBCG prognostic algorithm (no, one to two, and three or more risk factors). All patients received at least six induction instillations after index transurethral resection of bladder tumour. We used 3-month landmark stacked cumulative incidence and multivariable Cox regression models to assess the benefit from a maintenance course in terms of risk of recurrence and progression according to the IBCG risk groups stratification. RESULTS: Among 464 patients, 205 (44%) received BCG treatment and 259 (56%) received intravesical chemotherapy. The median (interquartile range) number of maintenance instillations was 9 (5-11). Over a median follow-up of 57 months, 139 (30%) patients had a recurrence. Patients with no IBCG risk factors had a similar risk of 5-year disease recurrence according to treatment duration (7.7% vs 7.3%; hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.49-1.37, for induction only vs induction plus maintenance, respectively), whereas patients with one to two (5-year risk: 16% vs 13%; HR 0.65, 95% CI 0.48-0.82) or three or more IBCG risk factors (5-year risk: 21% vs 17%; HR 0.48, 95% CI 0.25-0.85) were associated with lower hazards of recurrence if treated with an induction plus maintenance course. CONCLUSIONS: The IBCG algorithm effectively stratifies patients with IR-NMIBC by recurrence risk. In this observational cohort, maintenance therapy was associated with lower recurrence rates in patients with one to two or three or more IBCG risk factors, but not in those with no risk factors. These findings suggest that the IBCG stratification may inform risk-adapted treatment decisions in patients with IR-NMIBC.	bladder
Role of radiotherapy in the management of bladder cancer: Recommendations of the Société française de radiothérapie oncologique, 2025 update.	We present the recommendations of the Société française de radiothérapie oncologie (SFRO; the French society for radiation oncology) regarding the indications and techniques for external beam radiotherapy for bladder cancer. Together with radical cystectomy, trimodal therapy for well-selected patients is one of the standard-of-care treatments in the management of localized muscle invasive bladder cancer, defined as a maximal trans-urethral resection of the bladder tumour, followed by radiotherapy and concomitant chemotherapy. Adjuvant radiotherapy is an option for patients with pathological high-risk bladder cancer. In the metastatic setting, consolidative radiotherapy is still under evaluation. Palliative radiotherapy using a hypofractionated regimen is a valid option in symptomatic patients.	bladder
Oncological outcome and survival predictors of widowed patients with bladder cancer in special populations.	This study aimed to identify prognostic indicators and develop a nomogram to predict the overall survival (OS) of widowed bladder cancer (WBCa) patients. WBCa patients between 2004 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into the training and validation sets at a 7:3 ratio. Independent prognostic factors were determined using univariate and multivariate Cox analyses. We constructed a nomogram to predict 3- and 5-year for WBCa patients based on the results of multivariate Cox regression analysis. Consistency index (C-index), receiving operating characteristic (ROC), and calibration curve were used to assess the predictive accuracy of the nomogram. Gender, age at diagnosis, ethnicity, histologic type, histologic grade, tumor‑node metastasis (TNM) stage, and surgery were identified as independent predictors of OS. The C-index value of the nomogram for predicting OS was 0.704 and 0.701 in the training and validation cohorts, respectively. The ROC curves and calibration plots indicated that the model was relatively accurate. Independent prognostic factors for WBCa patients were identified, and a nomogram was constructed to predict the 3- and 5-year OS. The model enables clinicians to determine cancer patients' survival prognosis and formulate personalized treatment plans.	bladder
Deep learning-based spatial analysis on tumor and immune cells of pathology images predicts MIBC prognosis.	OBJECTIVE: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. This study aims to explore the correlation between the spatial distribution of lymphocyte aggregates and the prognosis of MIBC using deep learning. METHODS: Whole-slide images (WSIs) and clinical information of MIBC patients were collected from The Cancer Genome Atlas (TCGA) and the HBlaU079Su01 microarray. After manually annotating tumor and lymphocyte aggregation regions, we developed an automated analysis pipeline, including segmentation and quality control of patches. A convolutional neural network (CNN) classification model was constructed. Based on the definition of the border region of tumor cell nests, we assessed 12 spatial indicators for different patch types within, around and outside the tumor cluster. Using multiomics, we explored the relationships among spatial indicators, clinical factors, the immune microenvironment and molecular mechanisms. RESULTS: We obtained 301 MIBC WSIs from the TCGA and 43 MIBC WSIs from the HBlaU079Su01 microarray. Two independent CNN models showed excellent classification performance in identifying patches containing tumor cells (AUC = 0.944, 95% CI: 0.942-0.945) and lymphoid aggregates (AUC = 0.934, 95% CI: 0.932-0.937) were constructed. Grad-CAM analysis revealed that some patches contained both tumor cells and lymphocytes. The prognostic value of Lymph_inside % was validated in the HBlaU079Su01 microarray. Multiomics analysis demonstrated that Lymph_inside % demonstrated significant positive correlations with antitumor immune cell abundance and the apoptosis pathway. CONCLUSIONS: Lymph_inside % can be an effective biomarker for predicting MIBC prognosis. This study suggests a novel approach for the development of new prognostic biomarkers based on the spatial distribution of lymphocyte aggregates.	bladder
FDA Approval Summary: Nogapendekin Alfa Inbakicept-pmln with BCG for BCG-Unresponsive Carcinoma In Situ.	On April 22, 2024, the U.S. FDA granted regular approval to nogapendekin alfa inbakicept-pmln (N-803) with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumors. Substantial evidence of effectiveness for this application was obtained from cohort A of the single-arm, multicenter QUILT-3.032 trial. Patients received N-803 400 μg administered intravesically with TICE BCG once a week for 6 weeks as induction therapy, a second induction course if complete response (CR) was not achieved at month 3, and maintenance N-803 with BCG weekly for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 maintenance doses). The major efficacy outcome measures were CR at any time [as defined by negative results for cystoscopy [with transurethral resection of bladder tumor (TURBT)/biopsies as applicable] per local investigator assessment and urine cytology] and duration of response. The CR rate in the 77-patient efficacy population, per FDA review, was 62% [95% confidence interval (CI), 51%-73%]. Of the 48 patients with a CR, 28 (58%; 95% CI, 26%-55%) and 19 (40%; 95% CI, 16%-36%) maintained a response for ≥12 months and ≥24 months, respectively. The most common adverse reactions were increased creatinine, dysuria, hematuria, urinary frequency, urinary urgency, and urinary tract infection. This article summarizes the data and FDA thought process supporting the approval of N-803 with BCG.	bladder
Development and landscape of maintenance therapy after first-line treatment of advanced or metastatic urothelial carcinoma.	Overall survival (OS) in patients with advanced or metastatic urothelial carcinoma (UC) is not optimistic. For a long time, the standard platinum-based chemotherapy has been one of the preferred treatment strategies. Despite the high initial objective response rate (ORR) to first-line chemotherapy in patients with metastatic UC, the rate of achieving complete response (CR) is low, and most patients will relapse within one year after first-line treatment. To further improve the OS of patients with metastatic UC, the success of the CheckMate901 and EV302 studies has brought new therapeutic options for the first-line treatment of these patients. Maintenance or consolidation therapy after first-line treatment is also important to improve the OS of patients with advanced UC. Maintenance therapy after first-line treatment of metastatic UC has undergone a long period of development until the success of the JAVELIN Bladder100 study. For the first time, this study established the application of avelumab as maintenance therapy after first-line platinum-containing chemotherapy. The aim of this paper is to review the development process of avelumab-based maintenance therapy after first-line treatment of advanced or metastatic UC and explore future options for maintenance therapy in patients with advanced or metastatic UC in the light of new first-line treatment options.	bladder
Genetic profiling of upper tract urothelial carcinoma: A necessity for precision medicine.	INTRODUCTION: The urothelium of the upper tract (renal pelvis and ureter) has morphological and functional similarities to the bladder. There are also morphological similarities between the urothelial carcinoma of the upper tract (UTUC) and the bladder (UCB). However, there are differences in the embryological origin, phenotype, disease course, and response to treatment between the upper tract and bladder urothelium and their corresponding malignancies. Comprehensive genomic studies can provide valuable information about the differences between UTUC and UCB, which have diagnostic and therapeutic implications. AREAS COVERED: In this study, we have collected and compared the available literature on the next-generation sequencing (NGS) of the UTUC and compared it to UCB with a focus on the effect of genomic changes on the disease course and management. The review revealed the value of NGS in providing important information for diagnosis and management, which can result in more successful precision medicine. EXPERT OPINION: Although there are shared gene alterations between UTUC and UCB, the presence of minor genomic variations between the two site differences in the genomic alterations can explain differences in disease course. An upfront knowledge of the molecular alterations in UTUC can provide valuable information for patient care.	bladder